Roflumilast is a PDE4 inhibitor for severe COPD with chronic bronchitis.
Also known as: daliresp, daxas
DailyMed/FDA — Daliresp; EMC-UK — Roflumilast
DailyMed/FDA; EMC-UK
Potent CYP3A4 inhibitor + CYP3A4 substrate: ritonavir increases roflumilast and metabolite levels.
Roflumilast is metabolised by CYP3A4 and CYP1A2 to roflumilast N-oxide (active metabolite, 3-5x more potent). Ritonavir potently inhibits CYP3A4, drastically increasing exposure to both roflumilast and N-oxide. The combination is contraindicated in EMA/FDA guidelines. Risk of severe GI toxicity (diarrhoea, nausea), hepatotoxicity, and excessive weight loss. Alternative in HIV patients: montelukast (not CYP-metabolised) or inhaled corticosteroid.
Ritonavir inhibits CYP3A4 — increases roflumilast and active metabolite levels. CONTRAINDICATED.
Roflumilast is metabolised by CYP3A4 and CYP1A2. Ritonavir potently inhibits CYP3A4, increasing roflumilast and its active metabolite (N-oxide) levels. Risk of GI and hepatic toxicity.
Liver function, signs of GI toxicity.
Severe hepatic toxicity.
CONTRAINDICATED. Do not co-administer. Consider alternative (e.g. montelukast).
DailyMed/FDA; EMC-UK
CYP3A4 inhibitor + CYP3A4 substrate: fluconazole may increase roflumilast levels.
Fluconazole inhibits CYP3A4, one of the metabolic pathways for roflumilast. Roflumilast and N-oxide metabolite levels may increase 20-30%. Monitor GI adverse effects (diarrhoea, nausea) and liver function. Reduce dose if necessary.
Fluconazole inhibits CYP3A4, increasing roflumilast 20-30%. Monitor adverse effects.
Fluconazole inhibits CYP3A4, a partial metabolic pathway for roflumilast. Levels may increase 20-30%.
Liver function, GI signs.
Monitor GI and hepatic adverse effects. Reduce dose if necessary.
DailyMed/FDA; EMC-UK
No documented food or drink interactions.
CONTRAINDICATED in severe hepatic impairment (Child-Pugh C). Significant exposure increase.
Do not administer in Child-Pugh B. Child-Pugh B: reduce dose.
DailyMed/FDA; EMC-UK
Roflumilast may cause or worsen depression. History of depression = higher risk.
Assess psychiatric history before starting. Monitor mood. Discontinue if significant depression.
DailyMed/FDA; EMC-UK
CONTRAINDICATED in pregnancy. Animal studies show reproductive toxicity.
CONTRAINDICATED in all trimesters.
Avoid during breastfeeding.
Reliable contraception is mandatory.
DailyMed/FDA; EMC-UK
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Anti-inflammatory activity via PDE4 inhibition. Reduces exacerbations in severe COPD.
Selectively inhibits phosphodiesterase 4 (PDE4), increasing intracellular cAMP levels in inflammatory cells (neutrophils, macrophages, eosinophils). Result: reduced neutrophilic airway inflammation and mucus hypersecretion.
Rapid oral absorption. Bioavailability: ~80%. Food does not affect Cmax but delays Tmax.
Metabolised by CYP3A4 and CYP1A2 to roflumilast N-oxide (active metabolite, 3-5x more potent). Weak CYP3A4 inhibitor.
Roflumilast: 17 h. N-oxide: 30 h.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
